Reviewed, UniProtKB/Swiss-Prot Q9BY41 (HDAC8_HUMAN)

Names and origin

Protein names

Recommended name:
    Histone deacetylase 8
      Short name=HD8
    EC=3.5.1.98

Gene names

Name:	HDAC8
Synonyms:	HDACL1
ORF Names:	CDA07

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	377 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes. Ref.1 Ref.2 Ref.3
Catalytic activity	Hydrolysis of an N(6)-acetyl-lysine residue of a histone to yield a deacetylated histone.
Subunit structure	Interacts with PEPB2-MYH11, a fusion protein consisting of the 165 N-terminal residues of CBF-beta (PEPB2) with the tail region of MYH11 produced by the inversion Inv(16)(p13q22), a translocation associated with acute myeloid leukemia of M4EO subtype. The PEPB2-MYH1 fusion protein also interacts with RUNX1, a well known transcriptional regulator, suggesting that the interaction with HDAC8 may participate in the conversion of RUNX1 into a constitutive transcriptional repressor. Interacts with CBFA2T3. Ref.7 Ref.8
Subcellular location	Nucleus. Note: Excluded from the nucleoli.
Tissue specificity	Weakly expressed in most tissues. Expressed at higher level in heart, brain, kidney and pancreas. Ref.2
Miscellaneous	Its activity is inhibited by trichostatin A (TSA) and butyrate, two well known histone deacetylase inhibitors.
Sequence similarities	Belongs to the histone deacetylase family. Type 1 subfamily.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Molecular function	Chromatin regulator Hydrolase Repressor
Technical term	3D-structure
Gene Ontology (GO)
Biological process	chromatin assembly or disassembly Ref.1 Traceable author statement. Source: ProtInc histone deacetylation Inferred from electronic annotation. Source: InterPro negative regulation of transcription from RNA polymerase II promoter Ref.1 Traceable author statement. Source: ProtInc transcription Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytoplasm Traceable author statement. Source: UniProtKB histone deacetylase complex Traceable author statement. Source: UniProtKB nuclear chromosome Ref.1 Traceable author statement. Source: ProtInc
Molecular function	histone deacetylase activity Ref.1 Traceable author statement. Source: UniProtKB transcription factor binding Traceable author statement. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9BY41-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q9BY41-2)

The sequence of this isoform differs from the canonical sequence as follows:
     248-272: LKEVYQAFNPKAVVLQLGADTIAGD → RTSCPKSRPVEAAAAACLPHLHSLV
     273-377: Missing.

Note: Derived from EST data.

Isoform 3 (identifier: Q9BY41-3)

The sequence of this isoform differs from the canonical sequence as follows:
     147-163: DEASGFCYLNDAVLGIL → RDVCVCGTLQGILKKSK
     164-377: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 377

377

Histone deacetylase 8

PRO_0000114708

Regions

Region

14 – 324

311

Histone deacetylase

Sites

Active site

143

1

By similarity

Natural variations

Alternative sequence

147 – 163

17

DEASG…VLGIL → RDVCVCGTLQGILKKSK in isoform 3.

VSP_007174

Alternative sequence

164 – 377

214

Missing in isoform 3.

VSP_007175

Alternative sequence

248 – 272

25

LKEVY…TIAGD → RTSCPKSRPVEAAAAACLPH LHSLV in isoform 2.

VSP_007176

Alternative sequence

273 – 377

105

Missing in isoform 2.

VSP_007177

Experimental info

Mutagenesis

142 – 143

2

HH → AA: Strongly reduces histone deacetylase activity. Ref.2

Sequence conflict

179

1

L → V Ref.4

Sequence conflict

223

1

R → W in AAF73428. Ref.2

Secondary structure

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377

Helix Strand Turn

Details...

Beta strand

17 – 19

3

Helix

22 – 28

7

Beta strand

31 – 34

4

Helix

37 – 47

11

Helix

50 – 53

4

Beta strand

54 – 57

4

Helix

64 – 67

4

Turn

68 – 70

3

Helix

73 – 85

13

Turn

91 – 97

7

Helix

108 – 127

20

Beta strand

132 – 136

5

Beta strand

153 – 155

3

Helix

157 – 165

9

Turn

166 – 168

3

Beta strand

172 – 176

5

Beta strand

178 – 180

3

Helix

183 – 189

7

Beta strand

193 – 202

10

Helix

220 – 222

3

Beta strand

226 – 231

6

Helix

237 – 255

19

Beta strand

258 – 263

6

Helix

281 – 292

12

Beta strand

297 – 301

5

Helix

308 – 323

16

Helix

337 – 340

4

Turn

341 – 343

3

Helix

359 – 373

15

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified April 11, 2003. Version 2. Checksum: CAA1B91894FB5013	FASTA	377	41,758
	10 20 30 40 50 60 MEEPEEPADS GQSLVPVYIY SPEYVSMCDS LAKIPKRASM VHSLIEAYAL HKQMRIVKPK 70 80 90 100 110 120 VASMEEMATF HTDAYLQHLQ KVSQEGDDDH PDSIEYGLGY DCPATEGIFD YAAAIGGATI 130 140 150 160 170 180 TAAQCLIDGM CKVAINWSGG WHHAKKDEAS GFCYLNDAVL GILRLRRKFE RILYVDLDLH 190 200 210 220 230 240 HGDGVEDAFS FTSKVMTVSL HKFSPGFFPG TGDVSDVGLG KGRYYSVNVP IQDGIQDEKY 250 260 270 280 290 300 YQICESVLKE VYQAFNPKAV VLQLGADTIA GDPMCSFNMT PVGIGKCLKY ILQWQLATLI 310 320 330 340 350 360 LGGGGYNLAN TARCWTYLTG VILGKTLSSE IPDHEFFTAY GPDYVLEITP SCRPDRNEPH 370 RIQQILNYIK GNLKHVV
	Isoform 2. Checksum: 060E9B19659F4A91	FASTA	272	29,944
	10 20 30 40 50 60 MEEPEEPADS GQSLVPVYIY SPEYVSMCDS LAKIPKRASM VHSLIEAYAL HKQMRIVKPK 70 80 90 100 110 120 VASMEEMATF HTDAYLQHLQ KVSQEGDDDH PDSIEYGLGY DCPATEGIFD YAAAIGGATI 130 140 150 160 170 180 TAAQCLIDGM CKVAINWSGG WHHAKKDEAS GFCYLNDAVL GILRLRRKFE RILYVDLDLH 190 200 210 220 230 240 HGDGVEDAFS FTSKVMTVSL HKFSPGFFPG TGDVSDVGLG KGRYYSVNVP IQDGIQDEKY 250 260 270 YQICESVRTS CPKSRPVEAA AAACLPHLHS LV
	Isoform 3. Checksum: 06E2B3E76A5D6B0D	FASTA	163	17,880
	10 20 30 40 50 60 MEEPEEPADS GQSLVPVYIY SPEYVSMCDS LAKIPKRASM VHSLIEAYAL HKQMRIVKPK 70 80 90 100 110 120 VASMEEMATF HTDAYLQHLQ KVSQEGDDDH PDSIEYGLGY DCPATEGIFD YAAAIGGATI 130 140 150 160 TAAQCLIDGM CKVAINWSGG WHHAKKRDVC VCGTLQGILK KSK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and characterization of a novel human class I histone deacetylase that functions as a transcription repressor." Hu E., Chen Z., Fredrickson T., Zhu Y., Kirkpatrick R., Zhang G.-F., Johanson K., Sung C.-M., Liu R., Winkler J. J. Biol. Chem. 275:15254-15264(2000) [PubMed: 10748112] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CHARACTERIZATION, FUNCTION. Tissue: Kidney.
[2]	"Cloning and characterization of a novel human histone deacetylase, HDAC8." Buggy J.J., Sideris M.L., Mak P., Lorimer D.D., McIntosh B., Clark J.M. Biochem. J. 350:199-205(2000) [PubMed: 10926844] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, FUNCTION, MUTAGENESIS OF 142-HIS-HIS-143. Tissue: Uterus.
[3]	"Cloning and characterization of human histone deacetylase 8." Van den Wyngaert I., de Vries W., Kremer A., Neefs J.-M., Verhasselt P., Luyten W.H.M.L., Kass S.U. FEBS Lett. 478:77-83(2000) [PubMed: 10922473] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CHARACTERIZATION, FUNCTION. Tissue: Heart.
[4]	"Characterization of a highly complex region in Xq13 and mapping of three isodicentric breakpoints associated with preleukemia." McDonell N., Ramser J., Francis F., Vinet M.-C., Rider S., Sudbrak R., Riesselman L., Yaspo M.-L., Reinhardt R., Monaco A.P., Ross F., Kahn A., Kearney L., Buckle V., Chelly J. Genomics 64:221-229(2000) [PubMed: 10756090] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[5]	"A novel gene expressed in human pheochromocytoma." Li Y., Huang Q., Peng Y., Song H., Yu Y., Xu S., Ren S., Chen Z., Han Z. Submitted (DEC-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). Tissue: Pheochromocytoma.
[6]	"The DNA sequence of the human X chromosome." Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C. , Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., Rogers J., Bentley D.R. Nature 434:325-337(2005) [PubMed: 15772651] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"ETO, a target of t(8;21) in acute leukemia, makes distinct contacts with multiple histone deacetylases and binds mSin3A through its oligomerization domain." Amann J.M., Nip J., Strom D.K., Lutterbach B., Harada H., Lenny N., Downing J.R., Meyers S., Hiebert S.W. Mol. Cell. Biol. 21:6470-6483(2001) [PubMed: 11533236] [Abstract] Cited for: INTERACTION WITH CBFA2T3.
[8]	"The inv(16) fusion protein associates with corepressors via a smooth muscle myosin heavy-chain domain." Durst K.L., Lutterbach B., Kummalue T., Friedman A.D., Hiebert S.W. Mol. Cell. Biol. 23:607-619(2003) [PubMed: 12509458] [Abstract] Cited for: INTERACTION WITH PEPB2-MYH11 FUSION PROTEIN.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

AF230097 mRNA. Translation: AAF73076.1.
AF245664 mRNA. Translation: AAF73428.1.
AJ277724 mRNA. Translation: CAB90213.1.
AA376331 mRNA. No translation available.
AI159768 mRNA. No translation available.
T99283 mRNA. No translation available.
AF212246 mRNA. Translation: AAK14930.1.
BX295542 Genomic DNA. No translation available.

IPI

IPI00245706.
IPI00515065.
IPI00747259.

RefSeq

NP_060956.1.

UniGene

Hs.310536

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1T64	X-ray	1.90	A/B	1-377	[»]
1T67	X-ray	2.31	A	1-377	[»]
1T69	X-ray	2.91	A	1-377	[»]
1VKG	X-ray	2.20	A/B	1-377	[»]
1W22	X-ray	2.50	A/B	1-377	[»]
2V5W	X-ray	2.00	A/B	1-377	[»]
2V5X	X-ray	2.25	A/B	1-377	[»]
3EW8	X-ray	1.80	A	1-377	[»]
3EWF	X-ray	2.50	A/B/C/D	1-377	[»]
3EZP	X-ray	2.65	A/B	1-377	[»]
3EZT	X-ray	2.85	A/B	1-377	[»]
3F06	X-ray	2.55	A/B	1-377	[»]
3F07	X-ray	3.30	A/B/C	1-377	[»]
3F0R	X-ray	2.54	A/B/C	1-377	[»]

ModBase

Search...

PTM databases

PhosphoSite

Q9BY41.

Proteomic databases

PRIDE

Q9BY41.

Genome annotation databases

Ensembl

ENSG00000147099. Homo sapiens. [Contig view]

GeneID

55869.

KEGG

hsa:55869.

Organism-specific databases

GeneCards

GC0XM071466.

H-InvDB

HIX0016870.

HGNC

HGNC:13315. HDAC8.

MIM

300269. gene.

PharmGKB

PA37766.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

Q9BY41.

OMA

Q9BY41. YHICESV.

Enzyme and pathway databases

Pathway_Interaction_DB

hdac_classi_pathway. Signaling events mediated by HDAC Class I.

Reactome

REACT_71. Gene Expression.

Gene expression databases

ArrayExpress

Q9BY41.

Bgee

Q9BY41.

CleanEx

HS_HDAC8.

GermOnline

ENSG00000147099. Homo sapiens.

Family and domain databases

InterPro

IPR000286. His_deacetylse.
IPR003084. His_deacetylse_1.
[Graphical view]

Gene3D

G3DSA:3.40.800.20. His_deacetylse. 1 hit.

PANTHER

PTHR10625. His_deacetylse. 1 hit.

Pfam

PF00850. Hist_deacetyl. 1 hit.
[Graphical view]

PIRSF

PIRSF037913. His_deacetylse_1. 1 hit.

PRINTS

PR01270. HDASUPER.
PR01271. HISDACETLASE.

ProtoNet

Search...

Other Resources

DrugBank

DB02546. Vorinostat.

NextBio

61182.

SOURCE

Search...

Entry information

Entry name

HDAC8_HUMAN

Accession

Primary (citable) accession number: Q9BY41
Secondary accession number(s): A6NET3, Q9NP76, Q9NYH4

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 11, 2003
Last sequence update:	April 11, 2003
Last modified:	June 16, 2009
This is version 69 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)